Bone sarcomas: ESMO-EURACAN-GENTURIS-ERN PaedCan Clinical Practice Guideline for diagnosis, treatment and follow-up

Key points

Key guideline recommendations

1. The initial work-up of a suspected primary bone sarcoma, including history, physical examination, imaging and biopsy, should be carried out at a sarcoma reference centre.

   IV, B

2. Pathological diagnosis should be made by a dedicated bone tumour pathologist according to the 2020 WHO classification and supported by ancillary investigations whenever relevant.

   IV, A

3. General staging to assess distant disease should include chest CT, bone scintigraphy and/or whole-body MRI and/or FDG-PET-CT/MRI as clinically indicated; baseline ALP and LDH should be measured in Ewing sarcoma and osteosarcoma.

   III, B

4. The accepted standard for bone sarcoma is treatment at reference centres and/or within reference networks with access to the full spectrum of care and age-specific expertise.

   III, A

5. Low-grade central and parosteal osteosarcomas, which have a low metastatic potential, should be treated by surgery alone.

   IV, B

6. Curative treatment of high-grade osteosarcoma consists of multimodal chemotherapy and surgery.

   II, A

7. Doxorubicin, cisplatin, high-dose methotrexate and ifosfamide are active in osteosarcoma [I, A]; in patients over 40, regimens combining doxorubicin, cisplatin and ifosfamide are preferred.

   III, B

8. Patients with primary metastatic osteosarcoma are treated with curative intent following the same principles as non-metastatic osteosarcoma.

   III, B

9. Treatment of recurrent osteosarcoma is primarily surgical for isolated lung metastases or local recurrence [IV, B]; second-line chemotherapy includes ifosfamide or cyclophosphamide, possibly with etoposide and/or carboplatin [III, B], and other active drugs such as gemcitabine and docetaxel [IV, C].

   IV, B

10. Molecular confirmation is mandatory to distinguish Ewing sarcoma from other round cell sarcomas.

    V, A

11. The interval-compressed VDC/IE regimen is currently the preferred first-line treatment in Ewing sarcoma.

    I, B

12. BuMel could be considered for selected patients with a poor response to VIDE induction and/or a tumour volume over 200 mL; the role of high-dose chemotherapy after interval-compressed VDC/IE has not been evaluated.

    I, B

13. Complete surgical excision, when feasible, is the best modality of local control in Ewing sarcoma, and radiotherapy alone is used when complete excision is not possible or would cause unacceptable morbidity.

    IV, A

14. Adjuvant radiotherapy (preoperative or postoperative) is indicated when the originally involved tissues cannot be completely resected with adequate margins, for large-volume tumours or a poor histological response [IV, B], and should be considered in non-sacral pelvic Ewing sarcoma regardless of margins, volume or response [II, B].

    IV, B

15. Chemotherapy regimens for relapsed Ewing sarcoma include alkylating agents with topoisomerase inhibitors, irinotecan with temozolomide, gemcitabine and docetaxel, high-dose ifosfamide or carboplatin with etoposide.

    III, B

16. Follow-up of high-grade bone sarcoma: roughly every 3 months in the first 2 years, every 6 months in years 3 to 5, every 6 to 12 months in years 5 to 10 and thereafter every 0.5 to 2 years; late effects should be monitored for more than 10 years.

    V, B

Study population

Endpoints

Safety and side effects

Clinical significance and place in guidelines

Limitations